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Molecular and Cellular Biology, July 2004, p. 6393-6402, Vol. 24, No. 14
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.14.6393-6402.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Global Nature of Dynamic Protein-Chromatin Interactions In Vivo: Three-Dimensional Genome Scanning and Dynamic Interaction Networks of Chromatin Proteins

Robert D. Phair,1 Paola Scaffidi,2 Cem Elbi,2 Jaromíra Vecerová,3 Anup Dey,4 Keiko Ozato,4 David T. Brown,5 Gordon Hager,2 Michael Bustin,2 and Tom Misteli2*

National Cancer Institute,2 National Institute of Child Health and Human Development, Bethesda, Maryland 20892,4 BioInformatics Services, Rockville, Maryland 20854,1 Institute of Experimental Medicine, Academy of Sciences of the Czech Republic and 1st Faculty of Medicine, Prague, Czech Republic,3 University of Mississippi Medical Center, Jackson, Mississippi 392165

Received 17 March 2004/ Returned for modification 18 April 2004/ Accepted 2 May 2004

Genome structure and gene expression depend on a multitude of chromatin-binding proteins. The binding properties of these proteins to native chromatin in intact cells are largely unknown. Here, we describe an approach based on combined in vivo photobleaching microscopy and kinetic modeling to analyze globally the dynamics of binding of chromatin-associated proteins in living cells. We have quantitatively determined basic biophysical properties, such as off rate constants, residence time, and bound fraction, of a wide range of chromatin proteins of diverse functions in vivo. We demonstrate that most chromatin proteins have a high turnover on chromatin with a residence time on the order of seconds, that the major fraction of each protein is bound to chromatin at steady state, and that transient binding is a common property of chromatin-associated proteins. Our results indicate that chromatin-binding proteins find their binding sites by three-dimensional scanning of the genome space and our data are consistent with a model in which chromatin-associated proteins form dynamic interaction networks in vivo. We suggest that these properties are crucial for generating high plasticity in genome expression.

* Corresponding author. Mailing address: National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Phone: (301) 402-3959. Fax: (301) 496-4951. E-mail: mistelit{at}mail.nih.gov.

Molecular and Cellular Biology, July 2004, p. 6393-6402, Vol. 24, No. 14
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.14.6393-6402.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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